Nature Immunology
3, 673 - 680 (2002)
Published online: 10 June 2002; | doi:10.1038/ni805
Human epithelial cells trigger dendritic cell−mediated allergic inflammation by producing TSLPVassili Soumelis1, Pedro A. Reche1, Holger Kanzler1, Wei Yuan1, Gina Edward1, Bernhart Homey1, 2, Michel Gilliet1, Steve Ho1, Svetlana Antonenko1, Annti Lauerma3, Kathleen Smith1, Daniel Gorman1, Sandra Zurawski1, Jon Abrams1, Satish Menon1, Terri McClanahan1, Rene de Waal-Malefyt1, Fernando Bazan1, Robert A. Kastelein1
& Yong-Jun Liu11
DNAX, 901 California Avenue, Palo Alto, CA 94304, USA. 2
Department of Dermatology, Heinrich-Hein University, Moorenstr. 5, 40225 Dusseldorf, Germany. 3
Department of Dermatology, Helsinki University Hospital, Meihlandentie 2, Helsinki, Finland.
Correspondence should be addressed to Yong-Jun Liu yong-jun.liu@dnax.orgWhether epithelial cells play a role in triggering the immune cascade leading to T helper 2 (TH2)-type allergic inflammation is not known. We show here that human thymic stromal lymphopoietin (TSLP) potently activated CD11c+ dendritic cells (DCs) and induced production of the TH2-attracting chemokines TARC (thymus and activation-regulated chemokine; also known as CCL17) and MDC (macrophage-derived chemokine; CCL22). TSLP-activated DCs primed naïve TH cells to produce the proallergic cytokines interleukin 4 (IL-4), IL-5, IL-13 and tumor necrosis factor- , while down-regulating IL-10 and interferon- . TSLP was highly expressed by epithelial cells, especially keratinocytes from patients with atopic dermatitis. TSLP expression was associated with Langerhans cell migration and activation in situ. These findings shed new light on the function of human TSLP and the role played by epithelial cells and DCs in initiating allergic inflammation.
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